Identification of H3N2 NA and PB1-F2 genetic variants and their association with disease symptoms during the 2014-15 influenza season.

The 2014-15 influenza season saw the emergence of an H3N2 antigenic drift variant that formed the 3C.2a HA clade. Whole viral genomes were sequenced from nasopharyngeal swabs of ninety-four patients with confirmed influenza A virus infection and primary human nasal epithelial cell cultures used to efficiently isolate H3N2 viruses. The isolates were classified by HA clade and the presence of a new set of co-selected mutations in NA (a glycosylation site, NAg+) and PB1-F2 (H75P). The NA and PB1-F2 mutations were present in a subset of clade 3C.2a viruses (NAg+F2P), which dominated during the subsequent influenza seasons. In human nasal epithelial cell cultures, a virus with the novel NAg+F2P genotype replicated less well compared with a virus with the parental genotype. Retrospective analyses of clinical data showed that NAg+F2P genotype viruses were associated with increased cough and shortness of breath in infected patients.

Assessing clinical investigators' perceptions of relevance and competency of clinical trials skills: An international AIDS Malignancy Consortium (AMC) study.

INTRODUCTION: The AIDS Malignancy Consortium (AMC) conducts clinical trials of therapeutic and prevention strategies for cancer in people living with HIV. With its recent expansion to Sub-Saharan Africa and Latin America, there was a need to increase the competence of clinical investigators (CIs) to implement clinical trials in these regions. METHODS: AMC CIs were invited to complete a survey to assess role-relevance and self-perceived competence based on the Joint Task Force for Clinical Trials Competency domains. RESULTS: A total of 40 AMC CIs were invited to complete the questionnaire and 35 responded to the survey. The data management and informatics and engaging with communities' domains were lowest in the average proportion of CIs rating themselves high (scores of 3-4) for self-perceived competency (46.6% and 44.2%) and role-relevance (61.6% and 67.5%), whereas, the ethical and participant safety considerations domain resulted in the highest score for competency (86.6%) and role-relevance (93.3%). In the scientific concepts and research design domain, a high proportion rated for competency in evaluating study designs and scientific literature (71.4% and 74.3%) but a low proportion for competency for designing trials and specimen collection protocols (51.4% and 54.3%). CONCLUSIONS: Given the complexity of AMC clinical research, these results provide evidence of the need to develop training for clinical research professionals across domains where self-perceived competence is low. This assessment will be used to tailor and prioritize the AMC Training Program in clinical trial development and management for AMC CIs.

Depsipeptide companeramides from a Panamanian marine cyanobacterium associated with the coibamide producer.

Two new cyclic depsipeptides, companeramides A (1) and B (2), have been isolated from the phylogenetically characterized cyanobacterial collection that yielded the previously reported cancer cell toxin coibamide A (collected from Coiba Island, Panama). The planar structures of the companeramides, which contain 3-amino-2-methyl-7-octynoic acid (Amoya), hydroxy isovaleric acid (Hiva), and eight α-amino acid units, were established by NMR spectroscopy and mass spectrometry. The absolute configuration of each companeramide was assigned using a combination of Marfey's methodology and chiral-phase HPLC analysis of complete and partial hydrolysis products compared to commercial and synthesized standards. Companeramides A (1) and B (2) showed high nanomolar in vitro antiplasmodial activity but were not overtly cytotoxic to four human cancer cell lines at the doses tested.

Validation of the Brazilian version of the Expanded Prostate Cancer Index Composite (EPIC) for patients submitted to radical prostatectomy.

OBJECTIVES: Validation of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire translated to Portuguese. This is an evaluation tool of the effects of treatment on quality of life of patients with prostate cancer. MATERIALS AND METHODS: In order to translate and validate, several recommended methodological techniques in the literature were included: initial translation, synthesis of translation, board committee review and back translation. Sample included 40 patients with localized prostate cancer submitted to surgical retropubic radical prostatectomy from 2008 to 2010. RESULTS: The internal consistency analysis of the scales of the questionnaire resulted in alpha Cronbach coefficients "very good" (> 0.9) and "good" (> 0.8) to 8 of 14 domains. The higher coefficients (0.94) were assigned to sexual score, subscales incontinence and sexual function. Post-operatory follow-up ranged from 3 to 35 months, median 18.7 months. CONCLUSIONS: The Brazilian version of EPIC is reliable and valid, and is a useful tool to evaluate the impact of retropubic radical prostatectomy on quality of life of Brazilian patients with localized prostate cancer, in national and internationals studies.

Validation of the Brazilian version of the Expanded Prostate Cancer Index Composite (EPIC) for patients submitted to radical prostatectomy

Objectives Validation of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire translated to Portuguese. This is an evaluation tool of the effects of treatment on quality of life of patients with prostate cancer. Materials and Methods In order to translate and validate, several recommended methodological techniques in the literature were included: initial translation, synthesis of translation, board committee review and back translation. Sample included 40 patients with localized prostate cancer submitted to surgical retropubic radical prostatectomy from 2008 to 2010. Results The internal consistency analysis of the scales of the questionnaire resulted in alpha Cronbach coefficients “very good” (> 0.9) and “good” (> 0.8) to 8 of 14 domains. The higher coefficients (0.94) were assigned to sexual score, subscales incontinence and sexual function. Post-operatory follow-up ranged from 3 to 35 months, median 18.7 months. Conclusions The Brazilian version of EPIC is reliable and valid, and is a useful tool to evaluate the impact of retropubic radical prostatectomy on quality of life of Brazilian patients with localized prostate cancer, in national and internationals studies. .

Is it safe and effective to treat complex renal cysts by the laparoscopic approach?

BACKGROUND AND PURPOSE: Bosniak III and IV renal cysts have low mortality potential, and little is reported regarding the feasibility and safety of managing such tumors by laparoscopy and its comparison with open surgery. We report on the experience with 37 complex renal cysts managed in the era of laparoscopy. PATIENTS AND METHODS: A retrospective analysis of a prospective database from all patients with renal tumors who were operated on at our institution was evaluated after Institutional Review Board approval. The database comprises information for demographic, clinical, imaging, preoperative, intraoperative, histologic, and follow-up data. A comparison among all performed approaches was done for demographic, American Society of Anesthesiologists classification, operative time, estimated blood loss, ischemia time, hospital stay, oncologic and survival rate. The cysts removed by laparoscopic partial nephrectomy were compared with the solid tumors removed by the same approach at the same period. RESULTS: The database included 407 patients with renal tumors who were operated on from 2000 to 2009 at our institution. In 36 patients of the total cohort, there were 37 complex renal cysts. No patients with preoperative Bosniak type I or II underwent surgery. Of the cysts, 60% were Bosniak IV, and 86% were confirmed as malignant; 40% were Bosniak III, and 44% were confirmed as malignant. Laparoscopic partial nephrectomy was performed in 67.5%. The tumor size and hospital stay were significantly different in the laparoscopic group. No cyst spillage occurred either by laparoscopy or by the open approach, and no tumor recurrence was found in a mean follow-up of 43.7 months with overall survival of 100%. CONCLUSION: Laparoscopic surgery for complex cysts is safe, feasible, and effective. Nevertheless, regardless of surgical approach, patients with complex renal cysts have excellent overall survival with short-term follow-up.

Coibamide A, a potent antiproliferative cyclic depsipeptide from the Panamanian marine cyanobacterium Leptolyngbya sp.

Coibamide A (1) is a new, potent antiproliferative depsipeptide which was isolated from a marine Leptolyngbya cyanobacterium collected from the Coiba National Park, Panama. The planar structure of 1 was elucidated by a combination of NMR spectroscopy and mass spectrometry. Exhaustive 1D and 2D NMR spectroscopy included natural abundance 15N and variable temperature experiments; mass spectrometry included TOF-ESI-MSn and FT-MSn experiments. Chemical degradation followed by chiral HPLC- and GC-MS analyses was used to assign the absolute configuration of 1. This highly methylated cyclized depsipeptide exhibited an unprecedented selectivity profile in the NCI 60 cancer cell line panel and appears to act via a novel mechanism.